癌細胞與材料表面的相互作用是生物界面化學研究中的前沿熱點之一，對腫瘤診斷,、抗癌藥物篩選等研究具有重要意義,。在國家自然科學基金委、科技部和中國科學院的大力支持下,，中國科學院化學研究所有機固體重點實驗室的科研人員，在生物界面上癌細胞的特異識別與粘附調控方面取得了重要進展,。
受免疫細胞與腫瘤細胞的特異粘附界面啟發(fā),，相關實驗人員不再將細胞簡化成理想的球體，而是還原其多尺度性,，提出了結構匹配和分子識別的協(xié)同細胞粘附的研究思路,，打破了傳統(tǒng)上僅僅對分子水平識別的局限，設計制備了與癌細胞結構尺寸匹配的硅納米線陣列表面,，有效提高了靶向腫瘤細胞的捕獲效率(Angew. Chem. Int. Ed. 2009,， 48,， 8970)，并將微流控技術和硅納米線細胞粘附界面相結合,，實現(xiàn)了高于97%的細胞捕獲效率(Angew. Chem. Int. Ed. 2011,， 50， 3084),。
在此基礎上,，研究人員將對血癌細胞特異性識別的核酸適配體修飾到硅納米線陣列上，建立了一個酶響應的“高捕獲易釋放”的細胞檢測平臺(Adv. Mater. 2011,， 23,， 4376)。為了建立更普適響應界面,，研究人員將生物相容性好的熱響應性的聚（N-異丙基丙烯酰胺）引入到硅納米線表面上,，實現(xiàn)了溫度響應的高效捕獲與有效釋放的癌細胞粘附可控界面(Adv. Mater. 2013，25,， 922,， 圖1)。該表面設計的獨特之處是利用牛血清蛋白易于吸附到疏水表面,，而在親水表面是去吸附的特點,。以牛血清蛋白為橋，介導癌細胞特異性抗體在界面上的吸附與去吸附,。而熱響應聚合物在體溫疏水,，室溫親水。這樣,，通過牛血清蛋白與界面之間的疏水相互作用,，就實現(xiàn)了抗體在表面的吸附和去吸附。相應的,，在體溫下就可以對癌細胞進行特異性識別粘附,，在室溫下可將捕獲的癌細胞釋放下來。另外,，牛血清蛋白本身有抗非特異粘附的特點,，從而降低了非靶向細胞的非特異粘附。該研究提供了一個無損的“高粘附易釋放”的細胞檢測平臺,，使捕獲后釋放細胞的存活率高達95.3 ± 1.2%,。
圖1 溫度響應的“高粘附易釋放”的癌細胞檢測平臺
進一步，研究人員通過表面引發(fā)的鏈轉移聚合反應將苯硼酸基聚合物刷引入到硅納米線表面,，制備了對pH值和葡萄糖雙重響應界面(J. Am. Chem. Soc. 2013,， 135， 7603,， 圖2),。當pH 6.8時,，苯硼酸聚合物與癌細胞表面的唾液酸殘基的結合常數遠大于苯硼酸聚合物與葡萄糖的結合常數，從而可以特異性癌細胞粘附,。而當pH值升高到7.8時,，苯硼酸聚合物與葡萄糖之間的結合常數大于其與唾液酸之間的結合常數，使粘附的癌細胞可以從表面釋放下來,。這樣通過改變pH值和葡萄糖濃度,，就實現(xiàn)了雙響應的癌細胞特異粘附和去粘附的有效調控。同時,，這個溫和調控過程對細胞沒有明顯的損傷,，細胞活性保持在95%以上。該研究為復雜生命體系中癌癥檢測與靶向藥物傳輸提供了理論基礎,。
圖2 利用不同pH值下苯硼酸聚合物對唾液酸和葡萄糖的結合常數的改變,，設計制備了pH值和葡萄糖雙重響應的癌細胞可控粘附納米界面
相關研究成果發(fā)表后引起了廣泛關注，被Wiley出版社選為Hot Topics,，并被MaterialsViews,、MaterialsViewsChina以及Global Medical Discovery作為新聞亮點進行了報道（生物谷Bioon.com）。
生物谷推薦的英文摘要
Advanced Materials doi: 10.1002/adma.201300888
Programmable fractal nanostructured interfaces for specific recognition and electrochemical release of cancer cells
Zhang P,， Chen L,， Xu T， Liu H,， Liu X,， Meng J， Yang G,， Jiang L,， Wang S.
Topographic recognition of cancer cells is triggered by fractal gold nanostructures (FAuNSs)， leading to dramatically enhanced recognition capability and efficient release of cancer cells with little damage. The unique characteristic of FAuNSs is the similar fractal dimension of their surface and that of a cancer cell. The design of fractal nanostructures will open up opportunities for functional design of bio-interfaces for highly efficient recognition and release of disease-related rare cells,， which will improve detection in a clinical environment.
Journal of the American Chemical Society DOI: 10.1021/ja401000m
Dual-Responsive Surfaces Modified with Phenylboronic Acid-Containing Polymer Brush To Reversibly Capture and Release Cancer Cells
Hongliang Liu ,， Yingying Li ， Kang Sun ,， Junbing Fan ,， Pengchao Zhang ， Jingxin Meng ,， Shutao Wang *,， and Lei Jiang
Artificial stimuli-responsive surfaces that can mimic the dynamic function of living systems have attracted much attention. However， there exist few artificial systems capable of responding to dual- or multistimulation as the natural system does. Herein,， we synthesize a pH and glucose dual-responsive surface by grafting poly(acrylamidophenylboronic acid) (polyAAPBA) brush from aligned silicon nanowire (SiNW) array. The as-prepared surface can reversibly capture and release targeted cancer cells by precisely controlling pH and glucose concentration,， exhibiting dual-responsive AND logic. In the presence of 70 mM glucose,， the surface is pH responsive,， which can vary from a cell-adhesive state to a cell-repulsive state by changing the pH from 6.8 to 7.8. While keeping the pH at 7.8,， the surface becomes glucose responsive—capturing cells in the absence of glucose and releasing cells by adding 70 mM glucose. Through simultaneously changing the pH and glucose concentration from pH 6.8/0 mM glucose to pH 7.8/70 mM glucose， the surface is dual responsive with the capability to switch between cell capture and release for at least 5 cycles. The cell capture and release process on this dual-responsive surface is noninvasive with cell viability higher than 95%. Moreover,， topographical interaction between the aligned SiNW array and cell protrusions greatly amplifies the responsiveness and accelerates the response rate of the dual-responsive surface between cell capture and release. The responsive mechanism of the dual-responsive surface is systematically studied using a quartz crystal microbalance,， which shows that the competitive binding between polyAAPBA/sialic acid and polyAAPBA/glucose contributes to the dual response. Such dual-responsive surface can significantly impact biomedical and biological applications including cell-based diagnostics， in vivo drug delivery,， etc.
